Tripodal amphiphilic pseudopeptidic nanovesicles as p-coumaric acid delivery systems for brain cancer cells

Abstract

Nanovesicles based on tripodal amphiphilic pseudopeptides are prepared as carriers for p-coumaric acid (p-CA) delivery. Loaded nanovesicles are obtained by both thin film hydration and ethanol injection methods with positive Z-potential values. The last technique renders lower particle sizes and excellent polydispersity index, with average values of 130 nm and 0.123, respectively, although the drug loading obtained after ultracentrifugation is lower. In vitro release experiments, including the use of different external stimuli such as pH and proteolytic enzymes, provide interesting results. The prepared nanovesicles are tested on normal cells (VERO), displaying a high safety profile scoring with a 50% inhibitory concentration (IC50) of 1,822 mg/mL. A 40-times increase in the in vitro cytotoxic effect of p-CA on Glioma GL261 brain cancer cells, from IC50 1,082 mg/mL to 29 mg/mL, is observed using the loaded pseudopeptide nanovesicles. 1 H NMR studies reveal that the drug is mainly located inside the nanoparticle bilayer. Transmembrane carboxyfluorescein studies reveal that the amphiphilic compound does not provide a significant membrane fluidification. Experimental data suggest that the observed biological activity can be associated to an enhanced permeability and retention effect. The present results highlight the potential of such nanovesicles as potent p-CA carriers for brain cancer therapy.